We are investigating mechanisms of drug resistance in E. coli, of which two principle areas are being developed. One area is that of expression of resistance. We are proceeding with studies of induction of TC resistance in which we have already showed that induction can be produced with very low TC concentrations (as low as 0.02 micrograms/ml) and that induction is a characteristic of all clinical TC-resistant isolates so far examined. We are also studying the mode of expression of in terms of the product produced by the plasmid. We are going to try to isolate the product so that we can determine why some plasmids produce greater TC resistance than do other plasmids. Another factor to consider is whether or not the location of the resistance genes is chromosomal or extrachromosomal. For those resistant cultures which do not transfer resistance we are going to determine the location of the resistance genes by attempting to mobilize the resistance and also to look for plasmid DNA. The other area is that of transfer of resistance. We have found that plasmids which produce high levels of resistance to TC have a greater propensity to transfer resistance than do those which produce low levels of resistance. We are going to further investigate the possible connection between resistance level and transfer. A requisite feature of transfer is pilus production, and we are going to label pili in order to measure the kinetics of pilus formation.